School of Medicine

Department of Genetics

Genetic Considerations of Diseases and Disorders that Affect the Oral Cavity part 2


Part II. Oral Cancer and Developmental Disorders

S. Michele Robichaux, D.D.S.

Cancers involve body tissues whose cells are dividing and growing faster than cells are dying. The result of excessive cell growth is an enlarged mass called a tumor. Cancers may fail to remain within the boundaries of normal tissues and therefore spread or invade surrounding healthy tissues. Unfortunately, cancer of the head and neck is diagnosed relatively frequently. The most common oral cancers involve the surface tissue (epithelium) of the mouth and pharynx.

Genetic Factors. Genetic factors involved in the development of cancer include:

  1. Hereditary predisposition. An individual with a hereditary predisposition for cancer is a person with an increased likelihood of developing cancer due to inherited genes. These inherited genes make body cells more sensitive to environmental factors, such as sunlight and tobacco, and, therefore change normal body cells into cancer cells.
  2. Oncogenes. Cancers can be derived from mutations in genes that change cell growth patterns. These genes are called oncogenes. Such a mutation in an oncogene can convert ordinary body cells into cancer cells. Cancers caused by oncogenes are not inherited. To date, scientists have discovered more than 100 oncogenes, and several oncogenes have been associated with cancers of the head and neck.
  3. Tumor suppressor genes. Normal tumor suppressor genes are anti-cancer genes that slow down or stop growth of normal body cells. Mutations of tumor suppressor genes can also cause the development of oral and pharyngeal cancers.

Tobacco and Alcohol. Use of tobacco and alcohol are the major risk factors for developing oral cancer. Tobacco and alcohol contains substances that are carcinogenic or promote cancer. Cigarettes smoke and substances in smokeless tobacco have received considerable attention as carcinogens that promote oral cancer. Studies also indicate that smoking in combination with consumption of alcohol produces an even greater risk for oral cancer than use of either substance alone.

Radiation. Radiation of high dosage and prolonged duration can produce cancer. There is no evidence that routine dental X-rays are carcinogenic, especially with today's high speed, low dosage machines.

Traumatic irritation. Prolonged irritation from broken teeth, rough dental restorations, and ill-fitting dentures are considered a possible causes for oral cancer.

Viruses. Some viruses can cause cancer in human cells. Studies have indicated a link to oral cancer with infections from herpes simplex type- I virus, Epstein-Barr virus, and human papillomavirus.

Early diagnosis is the single factor in successfully combating oral cancer. Therefore, it is crucial that the patient seeks immediate and proper treatment for the disease. If tissue of the mouth is suspected to be cancerous, a biopsy is necessary. A biopsy involves surgically removing diseased tissue for microscopic evaluation and diagnosis by a pathologist.

Pre-cancerous refers to early changes of normal cells that are changing into cancer cells. Recognition of pre-cancerous tissue of the mouth is an important role in the diagnosis and prevention of oral cancer by the dental health professional. Many times, pre-cancerous tissue goes unnoticed by an individual because it is not painful. As a general rule, pre-cancerous or early cancers do not heal.

Leukoplakia. Leukoplakia is a term that describes a 'white patch' on the surface of oral tissues. Leukoplakias have been associated with pre-cancerous tissues. In general, leukoplakias are suspected as pre- or early cancer if the white area cannot be scraped off the surface tissue and cannot be attributed to another disease.

Erythroplakia. Erythroplakia occurs in the oral cavity as a distinct and well-defined patch with a bright red and velvety surface. Erythroplakias are relatively rare lesions of the oral cavity. Erythroplakias are almost always pre-cancerous.

Cancers can involve growth changes to any tissue of the oral cavity. Cancers of the mouth may be benign or malignant tumors. A benign tumor is a mass limited within a connective tissue capsule. This type of tumor does not spread or invade adjacent tissue and is therefore usually not life-threatening. A malignant tumor, on the other hand, is a mass capable of spreading and invading other healthy tissues of the body. The spread of cancer cells occurs by traveling within the bloodstream or lymph system. A malignant tumor can then form additional sites of cancers away from the original tumor¾a process call metastasis. Malignant tumors are dangerous and difficult to control. Well-developed malignant cancers can be life threatening.

Squamous Cell Carcinoma. Squamous cell carcinoma is the most frequently occurring malignant cancer of the oral region. This type of cancer involves cell growth changes of the surface tissue of the oral region, the epithelium. Nearly 90% of all oral cancers are squamous cell carcinomas. The most frequent location of this cancer is on the lips, the tongue, and the floor of the mouth. A chronic (long-term) mouth ulcer that does not heal, a lesion attached to deeper tissues, and a red-velvety lesion are all suspect squamous cell carcinomas. If left untreated, squamous cell carcinomas undergo metastasis and involve vital organs of the body. Many times death is the result of complications to the heart and lungs.

Basal Cell Carcinoma. Basal cell carcinoma is a tumor located on the surface of skin that has hair. Basal cell carcinomas are associated with prolonged exposure of skin to the sun. Lesions initially appear as elevated blisters, followed by a period of ulceration and healing. Continued cycles of blistering, ulcerating, and healing of the same tissue occurs as deeper tissues are slowly invaded. Metastasis of basal cell carcinomas is rare; survival rate of individuals diagnosed with basal cell carcinoma is excellent.

Fibromas. Fibromas are benign tumors whose cell origin lies in the connective tissue supporting teeth within tooth sockets, the periodontal membrane.

Osteomas. Osteomas are benign tumors whose cell origin is the bone of the upper and lower jaw.

Malignant tumors of connective tissue origin. Malignant tumors of connective tissue origin (the periodontal membrane, bone and cartilage) include fibrosarcomas, osteosarcomas and chondrosarcomas.

Tumors of the teeth. Tumors involving cells of the teeth are termed odontogenic tumors.

Salivary gland tumors. Salivary gland tumors are varied in their degree of malignancy and tumor cell origin. Salivary gland tumors can be benign or malignant. This type of tumor is very rare.

The three major treatment considerations for oral cancer include:

  1. Surgical removal of diseased tissue. This is the best management for treatment of cancer if physically possible. The advantages for surgery are prompt treatment and the ability of physicians to study tissue removed during surgery with a microscope. With this study, it can be known that the entire tumor has been removed. The disadvantage of surgical treatment is normal tissue loss in the attempt to remove all diseased tissue. Another consequence to surgery is the risk of loss of function and cosmetic defects.
  2. Radiation therapy. This is an effective form of treatment for isolated areas of cancer. As the size of the tumors enlarge, larger doses of radiation are necessary to kill cancer cells. The advantages of radiation therapy are the preservation of normal tissues and the maintenance of normal tissue function. The major disadvantage of radiation therapy includes inflammation of the lining of the mouth, destruction of salivary gland tissue that can result in dry mouth, changes in taste sensations, dental decay, damage to small blood vessels, and the risk of necrosis to bone tissue.
  3. Chemotherapy. Chemotherapy is dependent on the cancer diagnosis. Therapy can be designed for a systemic approach (one that treats the entire body) or a regional approach (one that treats the only the area of the cancer). The appropriate medication and duration of treatment is determined by evaluating the location of the cancer and the severity of the disease process. There are many side effects to chemotherapy, including complications affecting cells of the bone marrow, the gut, and lining of the mouth.

Treatment of most cancers of the head and neck involve a combination of surgery, radiation and chemotherapy.

Developmental disorders of the head (craniofacial region) are the result of problems that occur during development and growth of a baby prior to birth. Genes responsible for formation of the head very early in pregnancy (approximately three weeks following conception) are also responsible for the development of limbs and vital organs, such as the heart and lungs. Therefore, craniofacial defects are many times components of other developmental defects. Many studies conclude that developmental defects result from the interaction of multiple genes and environmental factors.

Cleft Lip and Cleft Palate. The most common of all craniofacial defects is the cleft lip and cleft palate. Clefting, or incomplete fusion of the lip and/or palate, can occur alone or as part of a hereditary syndrome. The pattern of inheritance in cleft lip and cleft palate suggests that up to twenty genes are involved with this defect.

Craniosynostoses. Craniosynostoses is a genetic disorder that causes early fusion of the bones that surround and protect the brain (bones of the skull). As a result, dangerous amounts of pressure are created against an enlarging brain within a braincase that is not growing. Several hereditary syndromes include mental retardation due to craniosynostoses as a characteristic feature.

Hereditary Anodontia. Conditions of the complete absence of teeth (anodontia) have been correlated to specific genes. The complete absence of teeth alters bone development within the upper and lower jaws of the mouth.

Amelogenesis Imperfecta and Dentinogenesis Imperfecta. Amelogenesis imperfecta is a genetic disorder that results in defective enamel formation of teeth. Enamel is the hard surface covering the crowns of teeth. Amelogenesis imperfecta either causes problems in enamel hardening (mineralization) of normal amounts of enamel or causes a smaller amount of normal enamel to be produced. Dentinogenesis imperfecta is a genetic disorder that results in defective dentin formation within teeth. Dentin is a mineralized material forming the bulk of each tooth. Defective dentin causes the normal enamel layer that covers it to flake off. In both diseases, the teeth are weak and very sensitive to temperature and pressures. Amelogenesis imperfecta and dentinogenesis imperfecta are linked to defects in structural genes that code for proteins necessary for the development of enamel and dentin.

Osteogenesis Imperfecta. Osteogenesis imperfecta is an inherited disease caused by mutations of genes that produce collagen. Collagen is an important substance within connective tissues of the body such as bone. Osteogenesis imperfecta causes 'brittle bone' diseases that affect all bones of the body. A complication of osteogenesis imperfecta that involves tissues of the mouth in addition to the more generalized effect of fragile bones is a painful dentinogenesis imperfecta-like change in the teeth.

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HOW TO LEARN MORE This is the American Dental Association website, which provides access to news and publications related to dental health This is the American Association of Oral and Maxillofacial Surgeon website, which contains information about oral and maxillofacial surgery including oral cancer. This site provides diagnosis and treatment for cancers of the head and neck. This is the Cleft Lip and Palate Association website, which provides information and support to anyone with or affected by cleft lip and clept palate This is the American Cleft Palate-Craniofacial Association website. This national organization provides lay and professional services for cleft lip, cleft palate, and other craniofacial defects.

S. Michele Robichaux, D.D.S is an assistant professor of biology at Nicholls State University in Thibodaux, Louisiana. She teaches Human Anatomy, Physiology and Histology. Her research interests include the genetics and microbiology of periodontal disease. Dr. Robichaux also practices General Dentistry in Thibodaux, LA.

Dr. S. Michele Robichaux
Department of Biological Sciences
Nicholls State University
Thibodaux, LA 70310
(985) 448-4721